Aquaporin-1 in blood vessels of rat circumventricular organs.

Although the water channel protein aquaporin-1 (AQP1) is widely observed outside the rat brain in continuous, but not fenestrated, vascular endothelia, it has not previously been observed in any endothelia within the normal rat brain and only to a limited extent in the human brain. In this immunohistochemical study of rat brain, AQP1 has also been found in microvessel endothelia, probably of the fenestrated type, in all circumventricular organs (except the subcommissural organ and the vascular organ of the lamina terminalis): in the median eminence, pineal, subfornical organ, area postrema and choroid plexus. The majority of microvessels in the median eminence, pineal and choroid plexus, known to be exclusively fenestrated, are shown to be AQP1-immunoreactive. In the subfornical organ and area postrema in which many, but not all, microvessels are fenestrated, not all microvessels are AQP1-immunoreactive. In the AQP1-immunoreactive microvessels, the AQP1 probably facilitates water movement between blood and interstitium as one component of the normal fluxes that occur in these specialised sensory and secretory areas. AQP1-immunoreactive endothelia have also been seen in a small population of blood vessels in the cerebral parenchyma outside the circumventricular organs, similar to other observations in human brain. The proposed development of AQP1 modulators to treat various brain pathologies in which AQP1 plays a deleterious role will necessitate further work to determine the effect of such modulators on the normal function of the circumventricular organs.

Neurotoxicity of angiographic carbon dioxide in the cerebral vasculature.

RATIONALE AND OBJECTIVES: This study was undertaken to resolve conflicting evidence about the neurotoxicity of carbon dioxide gas as an angiographic contrast medium within the cerebral vasculature. MATERIALS AND METHODS: Single intracarotid injections or five consecutive intracarotid injections, at 2-minute intervals, of carbon dioxide, iopromide or saline, were given to 32 rabbits under clinically relevant conditions. Extravasation of Evans blue and Tc-pertechnetate was used to determine blood-brain barrier damage at 30 minutes or 6 hours after injection. At 6 hours after multiple injections, brains were removed for histologic examination. RESULTS: A single intracarotid injection of carbon dioxide caused minimal blood-brain barrier breakdown, whereas multiple injections caused significant breakdown that was still present at 6 hours after the injections. All carbon dioxide-injected brains that underwent histologic examination showed evidence of irreversible brain damage in the injected hemisphere. CONCLUSIONS: The study confirms the neurotoxicity of carbon dioxide within the cerebral vasculature and its unsuitability for clinical use in cerebral angiography.